Azacitidine Combined With Venetoclax and ATRA in Newly Diagnosed AML

Phase 3

Recruiting

• Conditions: Acute Myeloid Leukemia
• Interventions: Drug: Azacitidine Combined With Venetoclax and ATRA group

• Registration Number: NCT05654194
• Lead Sponsor: The First Affiliated Hospital of Soochow University

Brief Summary

This is a single arm study to evaluate the safety and efficiency of azacitidine (AZA) combination with venetoclax and ATRA in Patients With Newly diagnosed acute myeloid leukemia. Azacitidine, venetoclax and ATRA, may stop the growth of cancer cells, either by demethylation, by promoting cells differentiation or by killing the cells.

Detailed Description

This study include newly diagnosed AML patients who will accept the therapy with AZA combined with venetoclax and ATRA: (1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28, every 28 days for up to 2 cycles or progression; (2)Consolidate therapy:ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month till progression;

Study Timeline

• Study Start: 2022-10-31
• Status Verified: 2022-11
• Study First Submitted: 2022-11-25
• Study First Submitted QC: 2022-12-08
• Last Update Submitted: 2022-12-08
• Study First Posted: 2022-12-16
• Last Update Posted: 2022-12-16
• Primary Completion: 2023-03-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Newly diagnosed AML according to the WHO (2016) classification of acute myeloid leukemia.
• Age ≥ 18years.
• ECOG score: 0-3.
• White blood cell count ≤ 25*10^9/L
• Total bilirubin ≤ 3X the institutional upper limit of normal if attributable to hepatic infiltration by neoplastic disease
• AST (SGOT) and ALT (SGPT) ≤ 3X the institutional upper limit of normal
• Creatinine clearance ≥30ml/min

Exclusion Criteria

• Pregnancy or lactation.
• Acute promylocytic leukemia or chronic myeloid leukemia in blast crisis.
• Another malignant disease.
• Uncontrolled active infection.
• Left ventricular ejection fraction < 0.3 by echocardiography or grade III/IV cardiovascular dysfunction according to the New York Heart Association Classification.
• Active hepatitis B or hepatitis C infection.
• HIV infection.
• Other commodities that the investigators considered not suitable for the enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AVA（Azacitidine Combined With Venetoclax and ATRA）group	Azacitidine Combined With Venetoclax and ATRA group	(1)Inductive therapy: AZA 75mg/m² per day for days 1-7 and venetoclax 100mg orally for day 2 , 200mg orally for day 3, 300mg orally for day4-6, 400mg orally for day7-10,ATRA 45mg/m² for day 12-28,every 28 days for up to 2 cycles or progression; (2)Consolidate therapy:ATRA 45mg/m2 per day for d1-21 ,AZA 70mg/m² per day for days 1-7, every 28 days for up to 4 cycles or progression; (3) Maintenance therapy:ATRA 45mg/m2 for d1-21 every 28 days,AZA 70mg/m² per day for days 1-7, every 3 month untill progression;

Primary Outcome Measures

Name	Time	Method
Rate of the bone marrow complete response	after completion of one induction courses (1st Induction Course is 28 days) and before starting of the 2nd cycle	Rate of the bone marrow complete response after 1 cycle of inductive therapy include Rate of the bone marrow complete response included the rate of the including Complete Remission(CR) and Complete Remission with incomplete hematologic recovery (CRi) after 1 cycle of inductive therapy

Secondary Outcome Measures

Name	Time	Method
Number of adverse events	2 years	adverse events are evaluated with CTCAE V5.0.
Event Free Survival（EFS）	2 years	time from randomization to the relapse ,death or drug is unacceptably toxic
Rate of the bone marrow complete response after 2 cycle of inductive therapy	after completion of two induction courses (1st Induction Course is 28 days) and before starting of the 1st Consolidation cycle	Rate of the bone marrow complete response after 2 cycle of inductive therapy include Rate of the bone marrow complete response included the rate of the including Complete Remission(CR) and Complete Remission with incomplete hematologic recovery (CRi) after 2 cycle of inductive therapy
Minimal Residual Disease (MRD) response	after completion of two induction courses (one Course is 28 days) and before starting of the 1st Consolidation cycle	MRD response in bone marrow at the end of 2nd cycle
Overall Survival (OS)	2 years	time from randomization to death from any cause

Trial Locations

Locations (1)

the First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, China